Ca2+/calmodulin kinase

Other mechanisms have also been implicated in odor adaptation, including cAMP-dependent phosphorylation of ciliary proteins via protein kinase A G-protein-receptor kinase activity (GRK3), possibly via phosphorylation of the OR Ca2+/calmodulin kinase II (CaMKII) phosphorylation of ACIII cGMP and carbon monoxide [ 31 ]. These latter three mechanisms have been particularly linked to longer-lasting forms of adaptation, on the order of tens of seconds (for CaMKII) or minutes (CO/cGMP). Together with the short-term adaptation described above, these various molecular mechanisms provide the OSN with a number of ways to fine-tune odor responses over time. 

Mizuno, K., Ris, L., Sanchez-Capelo, A., Godaux, E. and Giese, K. P., 2006, Ca2+/Calmodulin Kinase Kinase alpha Is Dispensable for Brain Development But Is Required for Distinct Memories in Male, Though Not in Female, Mice, Mol Cell Biol, pp in press. 

Zhu WZ, Wang SQ, Chakir K, et al. Linkage of p,-adrenergic stimulation to apoptotic heart cell death through protein kinase A-independent activation of Ca2+/ calmodulin kinase II. J Clin Invest 2003 111 617-625. 

AMPK can also be activated by a Ca2+-mediated pathway involving phosphorylation at Thr-172 by the Ca2+/calmodulin-dependent protein kinase, CaMKK 3. CaMKKa and CaMKK 3 were discovered as the upstream kinase for the calmodulin-dependent protein kinases-1 and -IV they both activate AMPK in a Ca2+/ calmodulin-dependent manner in cell-free assays, although CaMKK 3 appears to much more active against AMPK in intact cells. Expression of CaMKKa and CaMKK(3 primarily occurs in neural tissues, but CaMKKp is also expressed in some other cell types. Thus, the Ca2+-mediated pathway for AMPK activation has now been shown to occur in response to depolarization in rat neuronal tissue, in response to thrombin (acting via a Gq-coupled receptor) in endothelial cells, and in response to activation of the T cell receptor in T cells. 

Benitez-King, G., Rios, A., Martinez, A. Anton-Tay, F. (1996). In vitro inhibition of Ca2+/calmodulin-dependent kinase n activity by melatonin. Biochim. Biophys. Acta 1290, 191-6. 

Bagni, C., Mannucci, L., Dotti, C. G., and Amaldi, F. (2000). Chemical stimulation of synaptosomes modulates alpha —Ca2+/calmodulin-dependent protein kinase II mRNA association to polysomes. J. Neurosci. 20, RC76. 

Takao, K., Okamoto, K., Nakagawa, T., Neve, R. L., Nagai, T., Miyawaki, A., Hashikawa, T., Kobayashi, S. and Hayashi, Y. (2005). Visualization of synaptic Ca2+/calmodulin-dependent protein kinase II activity in living neurons. J. Neurosci. 25, 3107-12. 

Secondary signals Glucose 6-phosphate activates synthesis. Ca2+-Calmodulin activates degradation by activating phosphorylase kinase. 

Ca2+,calmodulin-dependent May transiently associate with synaptic vesicles to phosphorylate synapsins and rabphilin-3A. May regulate various protein kinases I and II steps in neurotransmitter release. 

The Ca2+-calmodulin complex may also activate nitric oxide synthase (NOS), which binds to a PDZ domain of PSD-95. Activated NOS produces NO from arginine NO, in turn, activates guanylate cyclase, the enzyme that catalyzes the conversion of GTP to the intracellular messenger cGMP, which activates protein kinase G (PKG). 

FIGURE 21-6 Schematic illustration of the overall structure and regulatory sites of eleven different phosphodiesterase subtypes. The catalytic domain of the phosphodiesterases are relatively conserved, and the preferred substrate(s) for each type is shown. The regulatory domains are more variable and contain the sites for binding of Ca2+/calmodulin (CaM) and cGMP, as well as GAF and PAS domains. The regulatory domains also contain sites of phosphorylation by cAMP-dependent protein kinase (PKA). 

PDE1 is phosphorylated by Ca27calmodulin-dependent protein kinase II (CaM-kinase II), which results in decreased affinity of this enzyme for Ca2+/calmodulin and an increase in the concentration of Ca2+ needed for its activation. PDE1 is also phosphorylated by protein kinase A, which likewise decreases its binding to Ca27calmodulin. 

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